아데노신A수용체2B

Adenosine A2B receptor
아도라2B
식별자
별칭ADORA2B, ADORA2, 아데노신 A2b 수용체
외부 IDOMIM: 600446 MGI: 99403 HomoloGene: 20167 GeneCard: ADORA2B
직교체
인간마우스
엔트레스
앙상블
유니프로트
RefSeq(mRNA)

NM_000676

NM_007413

RefSeq(단백질)

NP_000667

NP_031439

위치(UCSC)Cr 17: 15.95 – 15.98MbChr 11: 62.14 – 62.16Mb
PubMed 검색[3][4]
위키다타
인간 보기/편집마우스 보기/편집

아데노신A 수용체(ADORA2B)는2B G단백질 결합 아데노신 수용체로, 이를 암호화하는 인간 아데노신A2b 수용체 유전자를 나타내기도 한다.[5]

메커니즘

이 일체형 막 단백질은 아데노신이 있는 곳에서 아데닐레이트 사이클라아제 활동을 자극한다.이 단백질은 액손 연장에 관여하는 네트린-1과도 상호작용한다.

유전자

이 유전자는 17번 염색체의 스미스 매거니스 증후군 지역 근처에 위치해 있다.[5]

리간즈

선택적 A2B 리간드에 대한 연구는 다른 세 가지 아데노신 수용체 하위 유형의 리간드 개발에 다소 뒤떨어졌지만, 현재 많은 A-선택적2B 화합물이 개발되었으며,[6][7][8][9][10][11][12][13][14][15] 이들의 잠재적 치료적 응용에 대한 연구가 진행 중이다.[16][17][18][19][20][21]

고민자

  • 베이 60-6583
  • NECA(N-ethylcarboxamidoadenosine)
  • (S)-PHPNECA - A에서2B 친화력과 효능이 높지만 다른 아데노신 수용체 하위 유형에 비해 선택성이 낮음
  • LUF-5835
  • LUF-5845 - 부분작용제

적대자와 역작용제

  • 복합 38:[22] 길항제, 높은 친화력 및 양호한 하위 유형 선택성
  • ISAM-140:[23] 비xantinic 선택적 길항제(Ki: 3.49nM)
  • ATL-801
  • CVT-6883
  • MISS-1706
  • MISS-1754
  • OSIP-339,3391
  • PSB-603
  • PSB-0788
  • PSB-115
  • PSB-1901:[24] 피코몰라 효과를 가진 길항제

참조

  1. ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000170425 - 앙상블, 2017년 5월
  2. ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000018500 - 앙상블, 2017년 5월
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: ADORA2B adenosine A2b receptor".
  6. ^ Volpini R, Costanzi S, Lambertucci C, Taffi S, Vittori S, Klotz KN, Cristalli G (July 2002). "N(6)-alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A(3) receptor and a starting point for searching A(2B) ligands". Journal of Medicinal Chemistry. 45 (15): 3271–9. doi:10.1021/jm0109762. PMID 12109910.
  7. ^ Volpini R, Costanzi S, Lambertucci C, Vittori S, Cristalli G (2002). "Purine nucleosides bearing 1-alkynyl chains as adenosine receptor agonists". Current Pharmaceutical Design. 8 (26): 2285–98. doi:10.2174/1381612023392856. PMID 12369946. Archived from the original on 2013-04-14.
  8. ^ Baraldi PG, Tabrizi MA, Preti D, Bovero A, Romagnoli R, Fruttarolo F, Zaid NA, Moorman AR, Varani K, Gessi S, Merighi S, Borea PA (March 2004). "Design, synthesis, and biological evaluation of new 8-heterocyclic xanthine derivatives as highly potent and selective human A2B adenosine receptor antagonists". Journal of Medicinal Chemistry. 47 (6): 1434–47. doi:10.1021/jm0309654. PMID 14998332.
  9. ^ Cacciari B, Pastorin G, Bolcato C, Spalluto G, Bacilieri M, Moro S (December 2005). "A2B adenosine receptor antagonists: recent developments". Mini Reviews in Medicinal Chemistry. 5 (12): 1053–60. doi:10.2174/138955705774933374. PMID 16375751. Archived from the original on 2013-04-14.
  10. ^ Baraldi PG, Romagnoli R, Preti D, Fruttarolo F, Carrion MD, Tabrizi MA (2006). "Ligands for A2B adenosine receptor subtype". Current Medicinal Chemistry. 13 (28): 3467–82. doi:10.2174/092986706779010306. PMID 17168717. Archived from the original on 2013-04-14.
  11. ^ Beukers MW, Meurs I, Ijzerman AP (September 2006). "Structure-affinity relationships of adenosine A2B receptor ligands". Medicinal Research Reviews. 26 (5): 667–98. doi:10.1002/med.20069. PMID 16847822. S2CID 24390495.
  12. ^ Elzein E, Kalla R, Li X, Perry T, Parkhill E, Palle V, Varkhedkar V, Gimbel A, Zeng D, Lustig D, Leung K, Zablocki J (January 2006). "Novel 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)-xanthine derivatives as high affinity and selective A2B adenosine receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 16 (2): 302–6. doi:10.1016/j.bmcl.2005.10.002. PMID 16275090.
  13. ^ Carotti A, Cadavid MI, Centeno NB, Esteve C, Loza MI, Martinez A, Nieto R, Raviña E, Sanz F, Segarra V, Sotelo E, Stefanachi A, Vidal B (January 2006). "Design, synthesis, and structure-activity relationships of 1-,3-,8-, and 9-substituted-9-deazaxanthines at the human A2B adenosine receptor". Journal of Medicinal Chemistry. 49 (1): 282–99. doi:10.1021/jm0506221. PMID 16392813.
  14. ^ Tabrizi MA, Baraldi PG, Preti D, Romagnoli R, Saponaro G, Baraldi S, Moorman AR, Zaid AN, Varani K, Borea PA (March 2008). "1,3-Dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives as highly potent and selective human A(2B) adenosine receptor antagonists". Bioorganic & Medicinal Chemistry. 16 (5): 2419–30. doi:10.1016/j.bmc.2007.11.058. PMID 18077171.
  15. ^ Stefanachi A, Brea JM, Cadavid MI, Centeno NB, Esteve C, Loza MI, Martinez A, Nieto R, Raviña E, Sanz F, Segarra V, Sotelo E, Vidal B, Carotti A (March 2008). "1-, 3- and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A2B adenosine receptor". Bioorganic & Medicinal Chemistry. 16 (6): 2852–69. doi:10.1016/j.bmc.2008.01.002. PMID 18226909.
  16. ^ Volpini R, Costanzi S, Vittori S, Cristalli G, Klotz KN (2003). "Medicinal chemistry and pharmacology of A2B adenosine receptors". Current Topics in Medicinal Chemistry. 3 (4): 427–43. doi:10.2174/1568026033392264. PMID 12570760. Archived from the original on 2013-04-14.
  17. ^ Gao ZG, Jacobson KA (September 2007). "Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs. 12 (3): 479–92. doi:10.1517/14728214.12.3.479. PMID 17874974. S2CID 13777846.
  18. ^ Kolachala V, Ruble B, Vijay-Kumar M, Wang L, Mwangi S, Figler H, Figler R, Srinivasan S, Gewirtz A, Linden J, Merlin D, Sitaraman S (September 2008). "Blockade of adenosine A2B receptors ameliorates murine colitis". British Journal of Pharmacology. 155 (1): 127–37. doi:10.1038/bjp.2008.227. PMC 2440087. PMID 18536750.
  19. ^ Haskó G, Linden J, Cronstein B, Pacher P (September 2008). "Adenosine receptors: therapeutic aspects for inflammatory and immune diseases". Nature Reviews Drug Discovery. 7 (9): 759–70. doi:10.1038/nrd2638. PMC 2568887. PMID 18758473.
  20. ^ Ham J, Rees DA (December 2008). "The adenosine a2b receptor: its role in inflammation". Endocrine, Metabolic & Immune Disorders Drug Targets. 8 (4): 244–54. doi:10.2174/187153008786848303. PMID 19075778. Archived from the original on 2013-04-14.
  21. ^ Kim MO, Kim MH, Lee SH, Suh HN, Lee YJ, Lee MY, Han HJ (June 2009). "5'-N-ethylcarboxamide induces IL-6 expression via MAPKs and NF-kappaB activation through Akt, Ca(2+)/PKC, cAMP signaling pathways in mouse embryonic stem cells". Journal of Cellular Physiology. 219 (3): 752–9. doi:10.1002/jcp.21721. PMID 19194991. S2CID 11066973.
  22. ^ Stefanachi A, Nicolotti O, Leonetti F, et al. (2008). "1,3-Dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines as potent A(2B) adenosine receptor antagonists: Design, synthesis, structure-affinity and structure-selectivity relationships". Bioorganic & Medicinal Chemistry. 16 (22): 9780–9. doi:10.1016/j.bmc.2008.09.067. PMID 18938084.
  23. ^ El Maatougui A, Azuaje J, González-Gómez M, Miguez G, Crespo A, Carbajales C, Escalante L, García-Mera X, Gutiérrez-de-Terán H, Sotelo E (2016). "Discovery of Potent and Highly Selective A2B Adenosine Receptor Antagonist Chemotypes". Journal of Medicinal Chemistry. 59 (5): 1967–1983. doi:10.1021/acs.jmedchem.5b01586. PMID 26824742.
  24. ^ Jiang J, Seel CJ, Temirak A, Namasivayam V, Arridu A, Schabikowski J, Baqi Y, Hinz S, Hockemeyer J, Müller CE (2019). "A2B Adenosine Receptor Antagonists with Picomolar Potency". Journal of Medicinal Chemistry. 62 (8): 4032–4055. doi:10.1021/acs.jmedchem.9b00071. PMID 30835463.

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